Introduction

Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of pathophysiology, ranging from hepatic steatosis, through non-alcoholic steatohepatitis (NASH) and hepatic fibrosis, and in rare cases resulting in cirrhosis and liver failure. Hepatic fibrosis in NASH is caused by excessive synthesis of extracellular matrix (ECM) proteins with hepatic stellate cells (HSCs) playing an integral role. Following activation, quiescent hepatic stellate cells (qHSCs) proliferate and transform to an activated phenotype, in which they increase production of ECM proteins. Hepatic fibrosis progresses over time with an increase in the number of activated HSCs and production of hepatic ECM proteins. Fibrosis in NASH is histologically described by the accumulation of ECM proteins in different hepatic acinar zones, with stage I fibrosis occurring in the centrilobular (CL) zone; stage II fibrosis also includes the periportal (PP) zone. The differential activation of HSCs during the progression of fibrosis in NASH has not been well characterized to date; we have used a mathematical model to better characterize this aspect of NASH.

AASLD Liver Meeting, November 9-13, 2018, San Francisco, CA

By Diane M Longo, Grant T Generaux, Christina Battista, Paul B. Watkins, Brett A. Howell, Scott Q. Siler